Separating atrial near fields and atrial far fields in simulated intra-atrial electrograms

The detailed characterization of complex forms of atrial flutter relies on the correct interpretation of intra-atrial electrograms. For this, the near field components, which represent the local electrical activity, are decisive. However, far field components arising from distant electrical sources in the atria can obscure the diagnosis. We developed a method to separate and characterize atrial near field and atrial far field components from bipolar intra-atrial electrograms. First, a set of bipolar electrograms was created by simulating different propagation scenarios representing common clinical depolarization patterns. Second, near and far fields were detected as active segments using a non-linear energy operator-based approach. Third, the maximum slope and the spectral power were extracted as features for all active segments. Active segments were grouped accounting for both the timing and the location of their occurrence. In a last step, the active segments were classified in near and far fields by comparing their feature values to a threshold. All active segments were detected correctly. On average, near fields showed 15.1x larger maximum slopes and 40.4x larger spectral powers above 100 Hz than far fields. For 135 active segments detected in 72 bipolar electrograms, 5.2% and 6.7% were misclassified using the maximum slope and the spectral power, respectively. All active segments were classified correctly if only one near field segment was assumed to occur per electrogram. The separation of atrial near and atrial far fields was successfully developed and applied to in silico electrograms. These investigations provide a promising basis for a future clinical study to ultimately facilitate the precise clinical diagnosis of atrial flutter.

Electrocardiographic and electrophysiological characteristics of idiopathic ventricular arrhythmias originating from the vicinity of tricuspid annulus

Electrocardiographic and electrophysiological characteristics of VAs originating from the vicinity of the TA are not fully understood. Hence, 104 patients (mean age 52.6 ± 17.9 years; 62 male) with VAs originating from the vicinity of the TA were enrolled. After electrophysiological evaluation and ablation, data were compared among those patients. The ECGs and the correction of the ECGs based on the long axis of the heart calculated from the chest X-Ray were also analyzed. VAs originating from the vicinity of TA had distinctive ECG characteristics that were useful for identifying the precise origin. Our localization algorithm adjusted by the angle between the cardiac long axis and the horizon was found to be accurate in predicting the exact ablation site in 92.3% (n = 96) cases. Logistic regression analysis showed fractionated electrograms, the magnitudes of the local atrial electrograms and a/V ratio were critical factors for successful ablation. Among the 104 patients with VAs, complete elimination could be achieved by RFCA in 96 patients (success rate 92.3%) during a follow-up period of 35.2 ± 19.6 months. This study suggests that the ablation site could be localized by ECG analysis adjusted by the angle between the cardiac long axis and the horizon. Fractionated electrograms, the magnitudes of the local atrial electrograms and a/V ratio were demonstrated to be critical factors for successful ablation.

“Trapped reentry” as a dormant source of acute focal arrhythmia and fractionated atrial electrograms under sinus rhythm

Background Diseased atria are characterised by functional and structural heterogeneities (e.g. dense fibrotic regions), which add to abnormal impulse generation and propagation, like ectopy and block. These heterogeneities are thought to play a role in the origin of complex fractionated atrial electrograms (CFAEs) under sinus rhythm (SR) in atrial fibrillation (AF) patients, but also in the onset and perpetuation (e.g. reentry) of this disorder. The underlying mechanisms, however, remain incompletely understood. Purpose To test the hypothesis that dense local fibrotic regions could create an electrically isolated conduction pathway in which reentry can be established via ectopy and block to become “trapped” (giving rise to CFAEs under SR), only to be “released” under dynamic changes at a connecting isthmus (causing acute focal arrhythmia (FA)). Methods The geometrical properties of such an electrically isolated pathway, under which reentry could be trapped and released, were explored in vitro using optogenetics by creating conduction blocks of any shape by means of light-gated depolarizing ion channels (CatCh) and patterned illumination. Insight from these studies was used for complementary computational investigation in virtual human atria to assess clinical translation and to provide deeper mechanistic insight. Results Optical mapping studies, in monolayers of CatCh-activated neonatal rat atrial cardiomyocytes, revealed that reentry could indeed be established and trapped by creating an electrically isolated pathway with a connecting isthmus causing source-sink mismatch. This proves that a tachyarrhythmia can exist locally with SR prevailing in the bulk of the monolayer. Next, it was confirmed under which conditions reentry could escape this pathway by widening of the isthmus (i.e. overcoming the source-sink mismatch), thereby converting this local dormant arrhythmic source into an active driver with global impact (i.e. acute monolayer-wide FA). This novel phenomenon was shown in circuits <0.7cm2, adding to their probability to exist in human atria. Computational 3D studies revealed that the conditions for “trapped reentry” and its release can indeed be realized in human atria. Unipolar epicardial pseudo-electrograms derived from these simulations showed CFAEs at the site of “trapped reentry” in coexistence with normal electrograms showing SR in the bulk of the atria. Upon release of the reentry through reduction of gap junctional coupling, acute FA occurred, affecting the complete atria as evidenced by wave front and electrogram visualization. Conclusion This study reveals that “trapped reentry”, a previously undesignated phenomenon, can explain the origin of two designated ones: the observation of CFAEs under SR and acute onset of FA. Further exploration of the concept of “trapped reentry” may not only expand our understanding of AF initiation and perpetuation, but also termination, including ablation strategies by site-directed targeting. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was funded by the European Research Council (Starting grant 716509) to D.A. Pijnappels